Treatment of allergic inflammatory diseases with bronchodilators and anti-inflammatory agents is based on allopathy. These therapeutic agents are temporarily effective in ameliorating symptoms of allergic diseases but cannot basically control allergic diseases, failing to fundamentally treat the diseases.
In this connection, environmental diseases, such as bronchial asthma, atopic skin diseases, and allergic rhinitis, are known as immune diseases and Th2 cells are well known to play a central role in causing allergic responses. When stimulated by an antigen in lymphocytes, CD4 T cells can be differentiated into various types of Th cells depending on cytokines recognized simultaneously by the cells. When the recognized cytokines are type 2 cytokines, such as thymic stromal lymphopoietin (TSLP) or IL-4, such cells are differentiated into Th2 to cause allergic responses.
In addition, it was confirmed that dendritic cells presenting antigens to CD4 T cells also respond to stimulation by TSLP and assist in the differentiation of Th2 cells. After the differentiated Th2 cells migrate to allergy-causing tissue sites, for example, in the lung or skin, cytokines secreted from the corresponding tissues also play an important in the activation of the cells.
Such cytokines include TSLP, IL-25, and IL-33. Among these cytokines, TSLP is likely to play the most effective role. It was also found that suppression of TSLP secretion from animal models makes the formation and activation of Th2 cells difficult, causing no disease in the animals. It was also reported that suppression of TSLP in animals afflicted with diseases is helpful in treating the diseases. Overall, TSLP is an important cytokine that are involved in both differentiation and activation of Th2 cells and the regulation of TSLP is recognized to be important in the treatment of allergic diseases.
Many therapeutic approaches targeting TSLP have been reported. For example, Korean Patent Publication No. 2008-0099330 discloses antibodies which neutralize human TSLP activity and methods for the treatment of human TSLP related disorders, such as asthma, atopic dermatitis, and allergic rhinitis. Further, Korean Patent Publication No. 2009-0088950 discloses TSLP-specific antibodies and uses thereof in the treatment of allergic inflammatory disorders.
Further, Korean Patent Publication No. 2015-0006639 discloses a pharmaceutical composition having the ability to inhibit TSLP secretion which contains a compound represented by Formula 1 or a pharmaceutically acceptable salt thereof as an active ingredient.